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Action mechanism elucidation of DNT, anti-prostatecancer agent from natural products

Research Project

Project/Area Number 24592417
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionMicrobial Chemistry Research Foundation

Principal Investigator

YAMAZAKI Yohko  公益財団法人微生物化学研究会, 微生物化学研究所 沼津支所, 研究員 (80342690)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords去勢抵抗性前立腺がん / アンドロゲンレセプター / 前立腺がん / 前立腺癌
Outline of Final Research Achievements

Endocrine therapy (androgen ablation) is the main treatment for advanced prostate cancer. Despite an initial efficacy of androgen deprivation therapy, prostate cancer progress within a few years from androgen-dependent to castration- resistant (CRPC) disease in most of the patients. Although AR still plays an essential role in CRPC, AR inhibitor is only an antagonist.
We hypothesized that a new type AR inhibitor could serve as a unique therapeutic agent for prostate cancer. To identify a new type AR inhibitor, we screened cultured broths of microorganisms and found that small molecule compound N-deoxynortryptoquivaline (DNT), a novel inhibitor of AR function, showed potent inhibition against androgen-dependent proliferation of LNCaP prostate cancer cells. DNT showed significant inhibition of AR nuclear translocation and against androgen-dependent proliferation of LNCaP cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (7 results)

All 2015 2014 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Androprostamines A and B, the new anti-prostate cancer agents produced by Streptomyces sp. MK932-CF8.2015

    • Author(s)
      Yamazaki Y, Someno T, Igarashi M, Kinoshita N, Hatano M, Kawada M, Momose I, Nomoto A.
    • Journal Title

      J. Antibiot.

      Volume: 68 Issue: 4 Pages: 279-285

    • DOI

      10.1038/ja.2014.135

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complete stereochemistry and preliminary structure-activity relationship of rakicidin A, a hypoxia-selective cytotoxin from Micromonospora sp.2014

    • Author(s)
      Oku N, Matoba S, Yamazaki YM, Shimasaki R, Miyanaga S, Igarashi Y.
    • Journal Title

      Journal of Natural Products

      Volume: 77 Issue: 11 Pages: 2561-2565

    • DOI

      10.1021/np500276c

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Antitumor activity of androprostamine: a new antitumor agent for castration-resistant prostate cancer2014

    • Author(s)
      山崎洋子、増田徹、川田学、百瀬功、野本明男
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Androprostamine: A new antitumor agent for castration-resistant prostate cancer

    • Author(s)
      山崎洋子 増田徹 川田学 百瀬功 野本明男
    • Organizer
      第72回日本癌学会学術集会
    • Place of Presentation
      パシフィコ横浜 (横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Androprostamine: A new antitumor agent for androgen-dependent prostate Cancer

    • Author(s)
      山崎洋子 増田徹 川田学 百瀬功 野本明男
    • Organizer
      9th Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association
    • Place of Presentation
      ハイアットリージェンシーマウイ(アメリカ)
    • Related Report
      2012 Research-status Report
  • [Presentation] rakicidin Aの全立体構造および構造活性相関

    • Author(s)
      的場翔平 奥直也 山崎洋子 嶋崎良子 宮永賢 五十嵐康弘
    • Organizer
      日本農芸化学会2013年度大会
    • Place of Presentation
      東北大学(宮城)
    • Related Report
      2012 Research-status Report
  • [Remarks] 微生物化学研究所 沼津支所

    • URL

      http://www.bikaken.or.jp/laboratories/numazu/achievements.html

    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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